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Mutations in the TSC1 and TSC2 tumor suppressor genes give rise to the neoplastic disorders tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis. Their gene products form a complex that is a critical negative regulator of mammalian target of rapamycin (mTOR) complex 1 (mTORC1) and cell growth. We recently found that the TSC1-TSC2 complex promotes(More)
Despite the prognostic importance of mitotic count as one of the components of the Bloom-Richardson grade, several studies have found that pathologists' agreement on the mitotic grade is fairly modest. Collecting a set of more than 4,200 candidate mitotic figures, we evaluate pathologists' agreement on individual figures, and train a computerized system for(More)
Estrogens play a pivotal role in the development and progression of prostate cancer (PCa). Their actions are mediated by estrogen receptors (ERs), particularly ERbeta in the prostate epithelium. With the discovery of ERbeta isoforms, data from previous studies that focused principally on the wild-type ERbeta (ERbeta1) may not be adequate in explaining the(More)
BACKGROUND The signaling pathways imposing hormonal control over adipocyte differentiation are poorly understood. While insulin and Akt signaling have been found previously to be essential for adipogenesis, the relative importance of their many downstream branches have not been defined. One direct substrate that is inhibited by Akt-mediated phosphorylation(More)
Oncolytic herpes simplex virus-1 (oHSV) vectors selectively replicate in tumor cells, where they kill through oncolysis while sparing normal cells. One of the drawbacks of oHSV vectors is their limited replication and spread to neighboring cancer cells. Here, we report the outcome of a high-throughput chemical library screen to identify small-molecule(More)
Metformin has emerged as a potential anticancer agent. Here, we demonstrate that metformin plays an anti-tumor role via repressing N-cadherin, independent of AMPK, in wild-type N-cadherin cancer cells. Ectopic-expression of N-cadherin develops metformin-resistant cancer cells, while suppression of N-cadherin sensitizes cancer to metformin. Manipulation of(More)
OBJECTIVE To evaluate the role of preoperative neutrophil-to-lymphocyte ratio (NLR) and absolute neutrophil count (ANC) in patients' prognosis with localized papillary renal cell carcinoma (pRCC). METHODS Data from 218 localized pRCC patients (T1-3 N0/+ M0), operated between 1991 and 2011 at two centers, were evaluated retrospectively. Univariable and(More)
AIMS The present study was to assess the reduction of right ventricular pacing (RVP) by pacemaker algorithms of Managed Ventricular Pacing (MVP) and Search AV+ (SAV+) interval over a period of 12 months. METHODS AND RESULTS A total of 385 patients indicated for a dual-chamber pacemaker (DC-PM) were enrolled in the prospective, randomized COMPARE study at(More)
Oncolytic herpes simplex virus (oHSV)-1-based vectors selectively replicate in tumor cells causing direct killing, that is, oncolysis, while sparing normal cells. The oHSVs are promising anticancer agents, but their efficacy, when used as single agents, leaves room for improvement. We hypothesized that combining the direct oncolytic and antiangiogenic(More)